1. Field of the Invention
The present invention relates to a method of judging eradication of Helicobacter pylori (H. pylori: Hp) which is considered to be one of the causes of gastric and duodenal disease by examining body fluids, such as blood samples to be tested. In recent years, furthermore, it has been suspected that H. pylori is associated with development of gastric cancer, The present invention relates to a method of quickly and easily judging if H. pylori still remains in a person infected with H. pylori after H. pylori eradicating therapy, by using body fluids such as blood samples. The invention is further related to a method of eradicating H. Pylori and to a method of treating gastric and duodenal ulcer by combining the above-mentioned method with a medicine which contains, as main active ingredients, a drug for suppressing gastric acid secretion and an antibiotic or an antibacterial agent.
2. Description of Related Art
In diagnosing the infection with H. pylori, it has been urged to develop a method of correctly measuring (diagnosing) the presence or absence (eradication) of H. pylori after H. pylori eradicating therapy. So far, the eradication of H. pylori has been judged relying upon bacterial culture, urease test and histopathological examination, which require the collection of samples by mucosal biopsy during gastroduodenoscopy, and detecting the bacteria based upon nucleic acids extracted from gastric biopsied samples or gastric juice by polymerase chain reaction (PCR) techniques. After the eradicating treatment, however, culture test and urease test exhibit decreased sensitivity, and false negative results often appear. In the microscopic analysis of tissues, furthermore, the sensitivity varies depending upon the degree of skill of pathological diagnosticians. Besides, the distribution of H. pylori in the stomach is not uniform. When the biopsied tissues are used as samples, therefore, H. pylori is not always contained in the biopsied tissues that are removed in a several number. Therefore, though infection with H. pylori should turn out to be positive, it often turns out to be false negative due to sampling error. The PCR method features a high sensitivity but permits false positive to appear due to dead bacteria or contaminated bacteria. Namely, the PCR is cumbersome and cannot be easily put into practice. Besides, these examinations noted above require endoscopic examination which is invasive and cannot be easily performed repetitively. Examination methods other than a PCR method have been widely employed, however, lacking sensitivity and leaving a high probability of developing false negative. The urea breath test does not require the endoscopic inspection. However, .sup.13 C-urea is expensive and, besides, an apparatus for measuring the mass of carbon dioxide including .sup.13 C (i.e., gas isotope ratio mass spectrometry) is very expensive, too. Only a small number of such machines exist in Japan accompanied by problem in economy and availability. It has been said that a drop in the anti-H. pylori titer in the blood works effectively for judging the eradication of H. pylori. Even when H. pylori is actually eradicated, however, a period of not shorter than half a year is required before the antibody titer decreases (e.g., the titer decreases after half a year to more than nine months have passed), leaving a problem in that the result is not quickly obtained. Most patients who are eradication-treated are usually shifted from inpatients who receive therapeutic treatment in a hospital into outpatients who receive therapeutic treatment by going to the hospital or who are examined by going to the hospital as their condition recover. In practice, however, very few people attend the hospital to get examined for more than half a year. It has therefore been urged to carry out the precise measurement within short periods of time. On the other hand, patients without eradication of H. pylori have great chances of developing diseases again such as gastric or duodenal ulcer and gastric cancer.
It has been desired to provide means for quickly judging the eradication of H. pylori by examining body fluids such as blood, which is an ordinarily employed-examination means, without using endoscopy, to objectively judge the eradication of H. pylori by simply utilizing a conventional examination device that has heretofore been widely used.
It has been known that pepsinogen is an inactive precursor of pepsin which is a proteolytic enzyme in the gastric juice, and turns into pepsin by removing a peptide at the N-terminal thereof. Immunologically, the pepsinogens can be classified into two groups of pepsinogen I (PG I) and pepsinogen II (PG II), and their distributions delicately differ depending upon the places in the living body. It has been known that the PG I value and the PG II value in the blood of patients infected with H. pylori are high and that these values decrease and the PG I/PG II ratios increase by eradication of H. pylori (Fred M. Hunter, et al., Digestive Dieases and Sciences, Vol. 38, No. 11, pp. 2081-2086, 1993). Since the basal values differ depending upon the individual patients, however, it is difficult, relying upon the value of serum pepsinogens, to determine whether eradication is accomplished or not. In practice, the PG I value in the blood and the PG II value in the blood vary depending upon the individual patients due to ages and environments in which they live. Besides, extension of atrophy of the stomach which affects pepsinogen values, not always corrected with age in every patients. Therefore, it is meaningless to use the measured values or to establish certain cut-off values.